Molecular Karyotyping in Anorectal Malformations: Could DGCR6 Gene Haploinsufficiency Cause Anal Atresia in 22q11 Deletion Syndrome?
1Department of Medical Genetics, Gazi University Faculty of Medicine, Ankara, Turkey; Department of Medical Genetics, University of Health Sciences, Haseki Training and Research Hospital, İstanbul, Turkey
2Department of Medical Genetics, Gazi University Faculty of Medicine, Ankara, Turkey
J Clin Pract Res 2022; 44(3): 299-305 DOI: 10.14744/etd.2021.58701
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Abstract

Objective: Anorectal malformations (ARM) are classified as a multifactorial disease. The etiology of ARM is still not clear due to the complexity of the pathological anomalies.
Materials and Methods: The microarray-based comparative genomic hybridization (array CGH) results of 10 patients with ARM not associated with a specific syndrome were analyzed using the 8x60K ISCA Agilent microarray platform (Human Genome CGH Microarray; Agilent Technologies, Inc., Santa Clara, CA, USA). Pathogenic copy number variants were fur-ther confirmed using fluorescence in situ hybridization or quantitative real-time polymerase chain reaction testing.
Results: Chromosome 22q11.2 deletion was detected in 2 patients. One of these patients had anal stenosis, minor cardiac abnormalities, and a small 0.89-Mb deletion. The second patient had anal atresia, immune deficiency, inguinal hernia, and a 2.7-Mb cryptic deletion. The overlapping genes in the deletion regions of the 2 patients were the DGCR5, DGCR6, and PRODH genes.
Conclusion: DGCR6 alters the expression of important genes such as TBX1 and affects neural crest migration. Given that ARM are caused by abnormalities in neural crest cell migration, it may be that these genes play a role in the etiology. To our knowledge, this is one of the smallest interstitial deletions in the chromosome 22q11.2 region to be published to date. Further research on the DGCR6 gene, which may be a candidate gene responsible for anal atresia, will clarify this point.